Doctoral Dissertation Improvement Award: Effect of Nutrition on Ovarian Aging

华盛顿大学的Baishakhi Basu将进行一项研究，旨在阐明孟加拉国妇女早期和晚期营养不良影响卵巢衰老和更年期的机制。这项研究的灵感来自于大量的证据，即在资源贫乏的环境中，女性经历更年期的年龄比在资源丰富的环境中发现的年龄早6个月。这种差异的潜在生物学原因尚不清楚。该研究的一个组成部分将调查胎儿和儿童时期的营养压力如何影响更年期过渡期间的月经周期。 这项研究的另一个组成部分将调查晚年的营养压力是否会降低更年期发生的年龄。这项研究的更广泛的影响将是阐明生命早期的营养和生命后期的营养压力影响女性生殖生物学和功能的机制。 这项研究将有可能确定哪些生物机制缩短了营养压力下妇女的生殖寿命。 第一个研究胎儿生命和儿童营养可能影响卵巢衰老过程的途径。 在过渡到绝经期，卵巢卵泡池的几乎耗尽反映在越来越不规则的月经周期。 这项研究假设，在生命早期的营养不良导致一个较小的卵泡池建立在胎儿的生活和/或加速卵泡池减少的速度。 任何一种影响都会导致卵巢卵泡池的过早耗尽，从而导致更早地过渡到更年期。 这项研究将利用先前收集的月经日历，对1974年严重饥荒之前、期间和之后出生的2,300名孟加拉国农村妇女进行研究。这些女性出生在参加了1974年社会经济调查的家庭中，因此通过检验1974年家庭财富与女性开始过渡到更年期的年龄之间的任何统计关联来检验这一假设。 第二部分检查女性是否经历了一种与压力相关的闭经（没有月经周期），这种闭经在卵泡池完全耗尽（真正的绝经）之前破坏了月经周期。 这种所谓的下丘脑性闭经与真正的绝经期难以区分，因此可能被误认为是真正的绝经期。 为了验证这一想法，巴苏将进行为期两个月的调查，调查对象是500名在过去9-15个月内停止骑自行车的孟加拉国农村妇女。 将对受试者提供的尿液样本进行激素标记物检测，以区分真正的绝经与下丘脑性闭经。

Baishakhi Basu of the University of Washington will conduct research that aims to clarify the mechanisms by which early life and late life undernutrition affects ovarian aging and menopause in Bangladeshi women. The study is inspired by the abundant evidence that the age at which women in resource-poor settings experience menopause is about 6 months earlier than what is found in resource-abundant settings. The underlying biological cause of this discrepancy is unknown. One component of the study will investigate how nutritional stress in fetal life and childhood affects menstrual cycles during the transition that leads to menopause. Another component of the research will investigate whether nutritional stress later in life decreases the age at which menopause occurs. The broader impact of this study will be to elucidate the mechanisms by which nutrition in early life and nutritional stress in later life affects the reproductive biology and function in women. The study will potentially identify which biological mechanisms shorten the reproductive lifespan for women under nutritional stress.The research has two distinct components. The first examines pathways through which fetal life and childhood nutrition may affect the process of ovarian aging. During the transition to menopause, the near depletion of the ovarian follicle pool is reflected by increasingly irregular menstrual cycles. This study hypothesizes that undernutrition during early-life leads to a smaller ovarian follicle pool established in fetal life and/or accelerates the rate at which the follicle pool is reduced. Either effect would result in an earlier depletion of the pool of ovarian follicles and, consequently, an earlier transition to menopause. The research will utilize previously collected menstrual calendars on 2,300 rural Bangladeshi women born before, during and after a severe famine in 1974. The women were born in households that participated in a 1974 socio-economic survey, so the hypothesis is examined by testing for any statistical associations between household wealth in 1974 and the age a woman starts transitioning to menopause. The second component examines whether women experience a type of stress-related amenorrhea (absence of menstrual cycles) that disrupts menstrual cycles before the pool of ovarian follicles is fully depleted (true menopause). This so-called hypothalamic amenorrhea is indistinguishable from, and therefore can be mistaken with, true menopause. To test this idea, Basu will conduct a two month long investigation with the participation of 500 rural Bangladeshi women who have stopped cycling in the past 9-15 months. Urinary specimens provided by the participants will be tested for a hormonal marker that distinguishes true menopause from hypothalamic amenorrhea.